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- Title
5-Fluorouracil enhances apoptosis sensitivity of T lymphocytes mediated by CD3ε.
- Authors
Cheng, Hong; Liu, Yanxin; Liu, Shilian; Zheng, Dexian
- Abstract
Previous studies by our laboratory have reported that the T cell receptor (TCR) TCR/CD3 complex could mediate activation as well as apoptosis of T lymphocytes. Two tyrosine residues in the ITAM (immuno-receptor tyrosine-based activation motifs) of CD3ε were required for apoptosis signalling of Jurkat T lymphocytes. Stable cell lines TJK and T3JK produced from CD8− Jurkat T lymphocytes by transfection with wild-type and mutant CD8ε (fusion of the extracellular and transmembrane domains of human CD8α to the intracellular domain of mouse CD3ε), were used with CD8− Jurkat T lymphocytes for studying the role of single intact CD3ε. 5-Fluorouracil (5-FU), a chemotherapeutic drug can induce cell death of many tumour cell lines. In the present experiments, we examined the expression of caspase-3, p53 and Bid in the three cell lines induced by 5-FU and/or anti-CD8 antibody. We found high expression of p53 during activation-induced cell death of TJK cells mediated by anti-CD8 antibody and apoptosis of TJK and T3JK induced by 5-FU, implicating p53 involvement in apoptosis of leukemia cells induced by anti-CD8 antibody and 5-FU. We also detected the active form of caspase-3 and Bid in apoptotic leukemia cells after treatment with 5-FU and/or anti-CD8 antibody, indicating that the drug and antibody induced cell death through caspase-3 and the signal pathway may involve the Bcl-2 protein family. Our results showed that combined treatment with 5-FU and anti-CD8 antibody could enhance the rate of apoptosis induced by 5-FU or anti-CD8 antibody through increased expression of p53 and by promoting activation of caspase-3 and Bid. This suggests that the combination of 5-FU and anti-CD8 antibody may play an important role in inducing apoptosis of leukemia cells. Copyright © 2004 John Wiley & Sons, Ltd.
- Publication
Cell Biochemistry & Function, 2004, Vol 22, Issue 3, p187
- ISSN
0263-6484
- Publication type
Article
- DOI
10.1002/cbf.1083